Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) significantly improve the prognosis of non-small cell lung cancer (NSCLC) with EGFR sensitizing mutation. Although third-generation EGFR-TKI osimertinib is demonstrated with superior efficacy compared with first-generation EGFR-TKIs, acquired resistance to EGFR-TKIs remains the bottleneck. The Chinese herbal medicine (CHM) Yiqi-Yangyin-Jiedu decoction (YYJD) has been proved to delay acquired resistance to first-generation EGFR-TKIs in CATLA study, but there is no high-level evidence for its effect when combined with osimertinib. This trial aims to examine the efficacy and safety of YYJD combined with osimertinib as first-line treatment for advanced NSCLC harboring EGFR sensitizing mutation.
Methods: This is a double-blind, multi-center, randomized controlled trial conducted in 8 hospitals in China. A total of 314 participants will be randomly assigned to the osimertinib plus YYJD group (O+YYJD) or the osimertinib plus placebo group (O+placebo). Treatment will last until disease progression or death. Patients diagnosed with stage IV NSCLC harboring EGFR exon 19 del or exon 21 L858R will be enrolled if they are in accordance with deficiency of Qi and Yin pattern, ready to take osimertinib as first-line treatment, aged 18 to 74 years old, and provide signed informed consent. The primary outcome is progression-free survival (PFS). The secondary outcomes include a comparison of overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL). The analysis will be on intention-to-treat and per-protocol subject analysis principles.
Discussion: The goal of this trial is to evaluate the efficacy and safety of YYJD when added to 3 osimertinib as first-line treatment for advanced NSCLC with EGFR sensitizing mutation.
Trial registration: Chictr.org.cn ChiCTR1900026748. Registered on 20th October 2019.